HRP20200309T1 - Oksa-diazaspiro spojevi koji imaju aktivnost protiv bola - Google Patents
Oksa-diazaspiro spojevi koji imaju aktivnost protiv bola Download PDFInfo
- Publication number
- HRP20200309T1 HRP20200309T1 HRP20200309TT HRP20200309T HRP20200309T1 HR P20200309 T1 HRP20200309 T1 HR P20200309T1 HR P20200309T T HRP20200309T T HR P20200309TT HR P20200309 T HRP20200309 T HR P20200309T HR P20200309 T1 HRP20200309 T1 HR P20200309T1
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- HR
- Croatia
- Prior art keywords
- oxa
- substituted
- unsubstituted
- diazadispiro
- diazaspiro
- Prior art date
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- 150000001875 compounds Chemical class 0.000 title claims 50
- 208000002193 Pain Diseases 0.000 title claims 5
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims 12
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims 12
- 229910052739 hydrogen Inorganic materials 0.000 claims 11
- 150000002431 hydrogen Chemical group 0.000 claims 10
- 239000001257 hydrogen Substances 0.000 claims 10
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 8
- 125000000217 alkyl group Chemical group 0.000 claims 6
- 125000000753 cycloalkyl group Chemical group 0.000 claims 6
- 125000003118 aryl group Chemical group 0.000 claims 5
- -1 (2S,6R)-9-Isopentyl-2-methyl-1-oxa-4,9-diazaspiro[5.6]dodecan-4-yl Chemical group 0.000 claims 4
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 claims 4
- 125000004432 carbon atom Chemical group C* 0.000 claims 4
- 125000000623 heterocyclic group Chemical group 0.000 claims 4
- 238000000034 method Methods 0.000 claims 4
- 229940100198 alkylating agent Drugs 0.000 claims 3
- 239000002168 alkylating agent Substances 0.000 claims 3
- 230000029936 alkylation Effects 0.000 claims 3
- 238000005804 alkylation reaction Methods 0.000 claims 3
- URXHWBWRXXCBDP-UHFFFAOYSA-N 7-benzyl-10-ethyl-4-oxa-7,10-diazadispiro[2.1.35.33]undecan-11-one Chemical compound C(C1=CC=CC=C1)N1CC2(OC3(CC3)C(N(C2)CC)=O)C1 URXHWBWRXXCBDP-UHFFFAOYSA-N 0.000 claims 2
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims 2
- 208000004454 Hyperalgesia Diseases 0.000 claims 2
- 229910052799 carbon Inorganic materials 0.000 claims 2
- 238000006243 chemical reaction Methods 0.000 claims 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims 2
- 229910052736 halogen Inorganic materials 0.000 claims 2
- 150000002367 halogens Chemical group 0.000 claims 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 2
- 150000003839 salts Chemical class 0.000 claims 2
- FYMBWHNLOVIMQZ-VQIMIIECSA-N (2R,6R)-10-benzyl-4-ethyl-2-methyl-1-oxa-4,10-diazaspiro[5.6]dodecan-3-one Chemical compound C(C1=CC=CC=C1)N1CC[C@@]2(CN(C([C@H](O2)C)=O)CC)CCC1 FYMBWHNLOVIMQZ-VQIMIIECSA-N 0.000 claims 1
- SDLMDCGHIYSNOS-DNVCBOLYSA-N (2R,6R)-4-ethyl-10-[(4-fluorophenyl)methyl]-2-methyl-1-oxa-4,10-diazaspiro[5.6]dodecan-3-one Chemical compound C(C)N1C([C@H](O[C@@]2(C1)CCN(CCC2)CC1=CC=C(C=C1)F)C)=O SDLMDCGHIYSNOS-DNVCBOLYSA-N 0.000 claims 1
- QCEAFOWTOSWFHK-NVXWUHKLSA-N (2R,6R)-4-ethyl-2-methyl-10-(3-methylbutyl)-1-oxa-4,10-diazaspiro[5.6]dodecan-3-one Chemical compound CCN1C[C@]2(CCCN(CCC(C)C)CC2)O[C@H](C)C1=O QCEAFOWTOSWFHK-NVXWUHKLSA-N 0.000 claims 1
- FYMBWHNLOVIMQZ-APWZRJJASA-N (2R,6S)-10-benzyl-4-ethyl-2-methyl-1-oxa-4,10-diazaspiro[5.6]dodecan-3-one Chemical compound C(C1=CC=CC=C1)N1CC[C@]2(CN(C([C@H](O2)C)=O)CC)CCC1 FYMBWHNLOVIMQZ-APWZRJJASA-N 0.000 claims 1
- SDLMDCGHIYSNOS-BEFAXECRSA-N (2R,6S)-4-ethyl-10-[(4-fluorophenyl)methyl]-2-methyl-1-oxa-4,10-diazaspiro[5.6]dodecan-3-one Chemical compound C(C)N1C([C@H](O[C@]2(C1)CCN(CCC2)CC1=CC=C(C=C1)F)C)=O SDLMDCGHIYSNOS-BEFAXECRSA-N 0.000 claims 1
- FYMBWHNLOVIMQZ-QFBILLFUSA-N (2S,6R)-10-benzyl-4-ethyl-2-methyl-1-oxa-4,10-diazaspiro[5.6]dodecan-3-one Chemical compound C(C1=CC=CC=C1)N1CC[C@@]2(CN(C([C@@H](O2)C)=O)CC)CCC1 FYMBWHNLOVIMQZ-QFBILLFUSA-N 0.000 claims 1
- SDLMDCGHIYSNOS-HNAYVOBHSA-N (2S,6R)-4-ethyl-10-[(4-fluorophenyl)methyl]-2-methyl-1-oxa-4,10-diazaspiro[5.6]dodecan-3-one Chemical compound C(C)N1C([C@@H](O[C@@]2(C1)CCN(CCC2)CC1=CC=C(C=C1)F)C)=O SDLMDCGHIYSNOS-HNAYVOBHSA-N 0.000 claims 1
- QCEAFOWTOSWFHK-DOTOQJQBSA-N (2S,6R)-4-ethyl-2-methyl-10-(3-methylbutyl)-1-oxa-4,10-diazaspiro[5.6]dodecan-3-one Chemical compound CCN1C[C@]2(CCCN(CCC(C)C)CC2)O[C@@H](C)C1=O QCEAFOWTOSWFHK-DOTOQJQBSA-N 0.000 claims 1
- FYMBWHNLOVIMQZ-LPHOPBHVSA-N (2S,6S)-10-benzyl-4-ethyl-2-methyl-1-oxa-4,10-diazaspiro[5.6]dodecan-3-one Chemical compound C(C1=CC=CC=C1)N1CC[C@]2(CN(C([C@@H](O2)C)=O)CC)CCC1 FYMBWHNLOVIMQZ-LPHOPBHVSA-N 0.000 claims 1
- SDLMDCGHIYSNOS-KXBFYZLASA-N (2S,6S)-4-ethyl-10-[(4-fluorophenyl)methyl]-2-methyl-1-oxa-4,10-diazaspiro[5.6]dodecan-3-one Chemical compound C(C)N1C([C@@H](O[C@]2(C1)CCN(CCC2)CC1=CC=C(C=C1)F)C)=O SDLMDCGHIYSNOS-KXBFYZLASA-N 0.000 claims 1
- QCEAFOWTOSWFHK-RDJZCZTQSA-N (2S,6S)-4-ethyl-2-methyl-10-(3-methylbutyl)-1-oxa-4,10-diazaspiro[5.6]dodecan-3-one Chemical compound CCN1C[C@@]2(CCCN(CCC(C)C)CC2)O[C@@H](C)C1=O QCEAFOWTOSWFHK-RDJZCZTQSA-N 0.000 claims 1
- NBGKEOUVHIEVLT-LJQANCHMSA-N (5R)-8-benzyl-13-ethyl-4-oxa-8,13-diazadispiro[2.1.65.33]tetradecan-14-one Chemical compound C(C1=CC=CC=C1)N1CC[C@]2(OC3(CC3)C(N(C2)CC)=O)CCC1 NBGKEOUVHIEVLT-LJQANCHMSA-N 0.000 claims 1
- NBGKEOUVHIEVLT-IBGZPJMESA-N (5S)-8-benzyl-13-ethyl-4-oxa-8,13-diazadispiro[2.1.65.33]tetradecan-14-one Chemical compound C(C1=CC=CC=C1)N1CC[C@@]2(OC3(CC3)C(N(C2)CC)=O)CCC1 NBGKEOUVHIEVLT-IBGZPJMESA-N 0.000 claims 1
- XKWNQRFKBYAEST-GFCCVEGCSA-N (6R)-2-(2,2-dimethylpropyl)-6-methyl-8-propan-2-yl-5-oxa-2,8-diazaspiro[3.5]nonan-7-one Chemical compound CC(C)N1CC2(CN(CC(C)(C)C)C2)O[C@H](C)C1=O XKWNQRFKBYAEST-GFCCVEGCSA-N 0.000 claims 1
- YSWCVTKMQYZIPN-LLVKDONJSA-N (6R)-2-(2,2-dimethylpropyl)-8-ethyl-6-methyl-5-oxa-2,8-diazaspiro[3.5]nonan-7-one Chemical compound CCN1CC2(CN(CC(C)(C)C)C2)O[C@H](C)C1=O YSWCVTKMQYZIPN-LLVKDONJSA-N 0.000 claims 1
- JREVQBMVAABLGI-CYBMUJFWSA-N (6R)-2-(3,3-dimethylbutyl)-6-methyl-8-propan-2-yl-5-oxa-2,8-diazaspiro[3.5]nonan-7-one Chemical compound CC(C)N1CC2(CN(CCC(C)(C)C)C2)O[C@H](C)C1=O JREVQBMVAABLGI-CYBMUJFWSA-N 0.000 claims 1
- HKHCVOSGVJTURA-GFCCVEGCSA-N (6R)-6-methyl-2-(2-methylpropyl)-8-propan-2-yl-5-oxa-2,8-diazaspiro[3.5]nonan-7-one Chemical compound CC(C)CN1CC2(C1)CN(C(C)C)C(=O)[C@@H](C)O2 HKHCVOSGVJTURA-GFCCVEGCSA-N 0.000 claims 1
- PLYZFQRZTOXMCP-CYBMUJFWSA-N (6R)-6-methyl-2-(3-methylbutyl)-8-propan-2-yl-5-oxa-2,8-diazaspiro[3.5]nonan-7-one Chemical compound CC(C)CCN1CC2(C1)CN(C(C)C)C(=O)[C@@H](C)O2 PLYZFQRZTOXMCP-CYBMUJFWSA-N 0.000 claims 1
- XAVVKQXXDMOIPL-LLVKDONJSA-N (6R)-8-ethyl-6-methyl-2-(2-methylpropyl)-5-oxa-2,8-diazaspiro[3.5]nonan-7-one Chemical compound C(C)N1C([C@H](OC2(CN(C2)CC(C)C)C1)C)=O XAVVKQXXDMOIPL-LLVKDONJSA-N 0.000 claims 1
- XKWNQRFKBYAEST-LBPRGKRZSA-N (6S)-2-(2,2-dimethylpropyl)-6-methyl-8-propan-2-yl-5-oxa-2,8-diazaspiro[3.5]nonan-7-one Chemical compound CC(C)N1CC2(CN(CC(C)(C)C)C2)O[C@@H](C)C1=O XKWNQRFKBYAEST-LBPRGKRZSA-N 0.000 claims 1
- YSWCVTKMQYZIPN-NSHDSACASA-N (6S)-2-(2,2-dimethylpropyl)-8-ethyl-6-methyl-5-oxa-2,8-diazaspiro[3.5]nonan-7-one Chemical compound CCN1CC2(CN(CC(C)(C)C)C2)O[C@@H](C)C1=O YSWCVTKMQYZIPN-NSHDSACASA-N 0.000 claims 1
- JREVQBMVAABLGI-ZDUSSCGKSA-N (6S)-2-(3,3-dimethylbutyl)-6-methyl-8-propan-2-yl-5-oxa-2,8-diazaspiro[3.5]nonan-7-one Chemical compound CC(C)N1CC2(CN(CCC(C)(C)C)C2)O[C@@H](C)C1=O JREVQBMVAABLGI-ZDUSSCGKSA-N 0.000 claims 1
- HKHCVOSGVJTURA-LBPRGKRZSA-N (6S)-6-methyl-2-(2-methylpropyl)-8-propan-2-yl-5-oxa-2,8-diazaspiro[3.5]nonan-7-one Chemical compound CC(C)CN1CC2(C1)CN(C(C)C)C(=O)[C@H](C)O2 HKHCVOSGVJTURA-LBPRGKRZSA-N 0.000 claims 1
- PLYZFQRZTOXMCP-ZDUSSCGKSA-N (6S)-6-methyl-2-(3-methylbutyl)-8-propan-2-yl-5-oxa-2,8-diazaspiro[3.5]nonan-7-one Chemical compound CC(C)CCN1CC2(C1)CN(C(C)C)C(=O)[C@H](C)O2 PLYZFQRZTOXMCP-ZDUSSCGKSA-N 0.000 claims 1
- XAVVKQXXDMOIPL-NSHDSACASA-N (6S)-8-ethyl-6-methyl-2-(2-methylpropyl)-5-oxa-2,8-diazaspiro[3.5]nonan-7-one Chemical compound C(C)N1C([C@@H](OC2(CN(C2)CC(C)C)C1)C)=O XAVVKQXXDMOIPL-NSHDSACASA-N 0.000 claims 1
- YGRVVPVTVHONDM-UHFFFAOYSA-N (7-benzyl-4-oxa-7,12-diazadispiro[2.1.55.33]tridecan-12-yl)-phenylmethanone Chemical compound C(C1=CC=CC=C1)N1CC2(OC3(CC3)CN(C2)C(=O)C2=CC=CC=C2)CCC1 YGRVVPVTVHONDM-UHFFFAOYSA-N 0.000 claims 1
- PNXFTPVSIZWETD-UHFFFAOYSA-N (8-benzyl-4-oxa-8,13-diazadispiro[2.1.65.33]tetradecan-13-yl)-phenylmethanone Chemical compound C(C1=CC=CC=C1)N1CCC2(OC3(CC3)CN(C2)C(=O)C2=CC=CC=C2)CCC1 PNXFTPVSIZWETD-UHFFFAOYSA-N 0.000 claims 1
- 125000006545 (C1-C9) alkyl group Chemical group 0.000 claims 1
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 1
- XAIGANLZIFWZNU-UHFFFAOYSA-N 10-benzyl-4-ethyl-2,2-dimethyl-1-oxa-4,10-diazaspiro[5.6]dodecan-3-one Chemical compound C(C1=CC=CC=C1)N1CCC2(CN(C(C(O2)(C)C)=O)CC)CCC1 XAIGANLZIFWZNU-UHFFFAOYSA-N 0.000 claims 1
- DDXWEXQXHKHAOS-UHFFFAOYSA-N 10-benzyl-4-ethyl-2,2-dimethyl-1-oxa-4,10-diazaspiro[5.6]dodecane Chemical compound C(C1=CC=CC=C1)N1CCC2(CN(CC(O2)(C)C)CC)CCC1 DDXWEXQXHKHAOS-UHFFFAOYSA-N 0.000 claims 1
- ZSPIWQUNBQTNJE-UHFFFAOYSA-N 10-benzyl-7-(2-phenylethyl)-4-oxa-7,10-diazadispiro[2.1.35.33]undecan-11-one Chemical compound O=C1N(Cc2ccccc2)CC2(CN(CCc3ccccc3)C2)OC11CC1 ZSPIWQUNBQTNJE-UHFFFAOYSA-N 0.000 claims 1
- YZMOXULPIFELJQ-UHFFFAOYSA-N 10-benzyl-7-(2-phenylethyl)-4-oxa-7,10-diazadispiro[2.1.35.33]undecane Chemical compound C(Cc1ccccc1)N1CC2(C1)CN(Cc1ccccc1)CC1(CC1)O2 YZMOXULPIFELJQ-UHFFFAOYSA-N 0.000 claims 1
- VDDXKVXCPGERFU-UHFFFAOYSA-N 10-ethyl-7-(3-methylbutyl)-4-oxa-7,10-diazadispiro[2.1.35.33]undecan-11-one Chemical compound C(C)N1CC2(OC3(CC3)C1=O)CN(C2)CCC(C)C VDDXKVXCPGERFU-UHFFFAOYSA-N 0.000 claims 1
- UBZXDWXCHACEIO-UHFFFAOYSA-N 12-benzyl-7-(2-methylpropyl)-4-oxa-7,12-diazadispiro[2.1.55.33]tridecane Chemical compound CC(C)CN1CCCC2(C1)CN(Cc1ccccc1)CC1(CC1)O2 UBZXDWXCHACEIO-UHFFFAOYSA-N 0.000 claims 1
- BXWGTAIMRHAYFP-UHFFFAOYSA-N 12-benzyl-7-(2-phenylethyl)-4-oxa-7,12-diazadispiro[2.1.55.33]tridecane Chemical compound C(Cc1ccccc1)N1CCCC2(C1)CN(Cc1ccccc1)CC1(CC1)O2 BXWGTAIMRHAYFP-UHFFFAOYSA-N 0.000 claims 1
- SELHOUCRISCRHS-UHFFFAOYSA-N 12-benzyl-7-(3-methylbutyl)-4-oxa-7,12-diazadispiro[2.1.55.33]tridecane Chemical compound CC(C)CCN1CCCC2(C1)CN(Cc1ccccc1)CC1(CC1)O2 SELHOUCRISCRHS-UHFFFAOYSA-N 0.000 claims 1
- AJFXVIWVABYZKI-UHFFFAOYSA-N 12-ethyl-7-(2-phenylethyl)-4-oxa-7,12-diazadispiro[2.1.55.33]tridecan-13-one Chemical compound C(C)N1CC2(OC3(CC3)C1=O)CN(CCC2)CCC1=CC=CC=C1 AJFXVIWVABYZKI-UHFFFAOYSA-N 0.000 claims 1
- VYTOZROCNATLRV-UHFFFAOYSA-N 12-ethyl-7-(2-phenylethyl)-4-oxa-7,12-diazadispiro[2.1.55.33]tridecane Chemical compound C(C)N1CC2(OC3(CC3)C1)CN(CCC2)CCC1=CC=CC=C1 VYTOZROCNATLRV-UHFFFAOYSA-N 0.000 claims 1
- HDJPUMZSBMSPRS-UHFFFAOYSA-N 12-ethyl-7-(3-methylbutyl)-4-oxa-7,12-diazadispiro[2.1.55.33]tridecan-13-one Chemical compound C(C)N1CC2(OC3(CC3)C1=O)CN(CCC2)CCC(C)C HDJPUMZSBMSPRS-UHFFFAOYSA-N 0.000 claims 1
- GNTWSAPEOXXFFA-UHFFFAOYSA-N 12-phenyl-7-(2-phenylethyl)-4-oxa-7,12-diazadispiro[2.1.55.33]tridecan-13-one Chemical compound C1(=CC=CC=C1)CCN1CC2(OC3(CC3)C(N(C2)C2=CC=CC=C2)=O)CCC1 GNTWSAPEOXXFFA-UHFFFAOYSA-N 0.000 claims 1
- MAMVFISTLKWMIL-UHFFFAOYSA-N 12-phenyl-7-(2-phenylethyl)-4-oxa-7,12-diazadispiro[2.1.55.33]tridecane Chemical compound C1(=CC=CC=C1)CCN1CC2(OC3(CC3)CN(C2)C2=CC=CC=C2)CCC1 MAMVFISTLKWMIL-UHFFFAOYSA-N 0.000 claims 1
- NCSZKRJYMKWGQJ-UHFFFAOYSA-N 13-benzyl-8-(2-methylpropyl)-4-oxa-8,13-diazadispiro[2.1.65.33]tetradecane Chemical compound CC(C)CN1CCCC2(CN(Cc3ccccc3)CC3(CC3)O2)CC1 NCSZKRJYMKWGQJ-UHFFFAOYSA-N 0.000 claims 1
- BTUSRHUYPSJRTQ-UHFFFAOYSA-N 13-benzyl-8-(2-phenylethyl)-4-oxa-8,13-diazadispiro[2.1.65.33]tetradecane Chemical compound C(Cc1ccccc1)N1CCCC2(CN(Cc3ccccc3)CC3(CC3)O2)CC1 BTUSRHUYPSJRTQ-UHFFFAOYSA-N 0.000 claims 1
- UGWDLTBSAXCOKY-UHFFFAOYSA-N 13-benzyl-8-(3-methylbutyl)-4-oxa-8,13-diazadispiro[2.1.65.33]tetradecane Chemical compound CC(C)CCN1CCCC2(CN(Cc3ccccc3)CC3(CC3)O2)CC1 UGWDLTBSAXCOKY-UHFFFAOYSA-N 0.000 claims 1
- JMXVNVOOMKQKMA-UHFFFAOYSA-N 13-ethyl-8-(2-phenylethyl)-4-oxa-8,13-diazadispiro[2.1.65.33]tetradecan-14-one Chemical compound C(C)N1CC2(OC3(CC3)C1=O)CCN(CCC2)CCC1=CC=CC=C1 JMXVNVOOMKQKMA-UHFFFAOYSA-N 0.000 claims 1
- QPCNRSSQYRKUAB-UHFFFAOYSA-N 13-ethyl-8-(2-phenylethyl)-4-oxa-8,13-diazadispiro[2.1.65.33]tetradecane Chemical compound C(C)N1CC2(OC3(CC3)C1)CCN(CCC2)CCC1=CC=CC=C1 QPCNRSSQYRKUAB-UHFFFAOYSA-N 0.000 claims 1
- ZPSGTLQPMDZCCC-UHFFFAOYSA-N 13-ethyl-8-(3-methylbutyl)-4-oxa-8,13-diazadispiro[2.1.65.33]tetradecan-14-one Chemical compound C(C)N1CC2(OC3(CC3)C1=O)CCN(CCC2)CCC(C)C ZPSGTLQPMDZCCC-UHFFFAOYSA-N 0.000 claims 1
- HAIVGHXFISHJHU-UHFFFAOYSA-N 13-phenyl-8-(2-phenylethyl)-4-oxa-8,13-diazadispiro[2.1.65.33]tetradecan-14-one Chemical compound C1(=CC=CC=C1)CCN1CCC2(OC3(CC3)C(N(C2)C2=CC=CC=C2)=O)CCC1 HAIVGHXFISHJHU-UHFFFAOYSA-N 0.000 claims 1
- CQDJVNJOMNGSPB-UHFFFAOYSA-N 13-phenyl-8-(2-phenylethyl)-4-oxa-8,13-diazadispiro[2.1.65.33]tetradecane Chemical compound C1(=CC=CC=C1)CCN1CCC2(OC3(CC3)CN(C2)C2=CC=CC=C2)CCC1 CQDJVNJOMNGSPB-UHFFFAOYSA-N 0.000 claims 1
- XNUFLAJRYKRRRS-UHFFFAOYSA-N 4-[(13-methyl-14-oxo-4-oxa-8,13-diazadispiro[2.1.65.33]tetradecan-8-yl)methyl]benzonitrile Chemical compound CN1CC2(CCCN(Cc3ccc(cc3)C#N)CC2)OC2(CC2)C1=O XNUFLAJRYKRRRS-UHFFFAOYSA-N 0.000 claims 1
- DEKYJSOSCLPAOR-UHFFFAOYSA-N 4-[(4-ethyl-2,2-dimethyl-3-oxo-1-oxa-4,10-diazaspiro[5.6]dodecan-10-yl)methyl]benzonitrile Chemical compound CCN1CC2(CCCN(Cc3ccc(cc3)C#N)CC2)OC(C)(C)C1=O DEKYJSOSCLPAOR-UHFFFAOYSA-N 0.000 claims 1
- YYLPDSFHMKRZDB-OXJNMPFZSA-N 4-[[(2S,6R)-4-ethyl-2-methyl-3-oxo-1-oxa-4,10-diazaspiro[5.6]dodecan-10-yl]methyl]benzonitrile Chemical compound CCN1C[C@]2(CCCN(Cc3ccc(cc3)C#N)CC2)O[C@@H](C)C1=O YYLPDSFHMKRZDB-OXJNMPFZSA-N 0.000 claims 1
- YYLPDSFHMKRZDB-JXFKEZNVSA-N 4-[[(2S,6S)-4-ethyl-2-methyl-3-oxo-1-oxa-4,10-diazaspiro[5.6]dodecan-10-yl]methyl]benzonitrile Chemical compound CCN1C[C@@]2(CCCN(Cc3ccc(cc3)C#N)CC2)O[C@@H](C)C1=O YYLPDSFHMKRZDB-JXFKEZNVSA-N 0.000 claims 1
- KQUCSWXNFBLLJR-UHFFFAOYSA-N 4-ethyl-2,2-dimethyl-10-(2-methylpropyl)-1-oxa-4,10-diazaspiro[5.6]dodecan-3-one Chemical compound CCN1CC2(CCCN(CC(C)C)CC2)OC(C)(C)C1=O KQUCSWXNFBLLJR-UHFFFAOYSA-N 0.000 claims 1
- FIRDTSDQTIUVPE-UHFFFAOYSA-N 4-ethyl-2,2-dimethyl-10-(2-methylpropyl)-1-oxa-4,10-diazaspiro[5.6]dodecane Chemical compound CCN1CC(C)(C)OC2(C1)CCCN(CC(C)C)CC2 FIRDTSDQTIUVPE-UHFFFAOYSA-N 0.000 claims 1
- SQHZCBRMZNDLHJ-UHFFFAOYSA-N 4-ethyl-2,2-dimethyl-10-(2-phenylethyl)-1-oxa-4,10-diazaspiro[5.6]dodecan-3-one Chemical compound CCN1CC2(CCCN(CCc3ccccc3)CC2)OC(C)(C)C1=O SQHZCBRMZNDLHJ-UHFFFAOYSA-N 0.000 claims 1
- FIQKVGYDSOXDQL-UHFFFAOYSA-N 4-ethyl-2,2-dimethyl-10-(2-phenylethyl)-1-oxa-4,10-diazaspiro[5.6]dodecane Chemical compound C(C)N1CC(OC2(C1)CCN(CCC2)CCC1=CC=CC=C1)(C)C FIQKVGYDSOXDQL-UHFFFAOYSA-N 0.000 claims 1
- JGQCTHNFZNXQHZ-UHFFFAOYSA-N 4-ethyl-2,2-dimethyl-10-(3-methylbutyl)-1-oxa-4,10-diazaspiro[5.6]dodecan-3-one Chemical compound CCN1CC2(CCCN(CCC(C)C)CC2)OC(C)(C)C1=O JGQCTHNFZNXQHZ-UHFFFAOYSA-N 0.000 claims 1
- LWQGRINXLZXMLE-UHFFFAOYSA-N 7,12-dibenzyl-4-oxa-7,12-diazadispiro[2.1.55.33]tridecane Chemical compound C(N1CCCC2(C1)CN(Cc1ccccc1)CC1(CC1)O2)c1ccccc1 LWQGRINXLZXMLE-UHFFFAOYSA-N 0.000 claims 1
- MRGZSTNJGNWTDF-UHFFFAOYSA-N 7-(3-methylbutyl)-12-phenyl-4-oxa-7,12-diazadispiro[2.1.55.33]tridecan-13-one Chemical compound C(CC(C)C)N1CC2(OC3(CC3)C(N(C2)C2=CC=CC=C2)=O)CCC1 MRGZSTNJGNWTDF-UHFFFAOYSA-N 0.000 claims 1
- GVJBAMUZSAONCE-UHFFFAOYSA-N 7-(3-methylbutyl)-12-phenyl-4-oxa-7,12-diazadispiro[2.1.55.33]tridecane Chemical compound C(CC(C)C)N1CC2(OC3(CC3)CN(C2)C2=CC=CC=C2)CCC1 GVJBAMUZSAONCE-UHFFFAOYSA-N 0.000 claims 1
- BNQJIYXAQQJPGR-UHFFFAOYSA-N 7-benzyl-12-ethyl-4-oxa-7,12-diazadispiro[2.1.55.33]tridecan-13-one Chemical compound C(C1=CC=CC=C1)N1CC2(OC3(CC3)C(N(C2)CC)=O)CCC1 BNQJIYXAQQJPGR-UHFFFAOYSA-N 0.000 claims 1
- NGYHVFUTMMQVBC-UHFFFAOYSA-N 7-benzyl-12-ethyl-4-oxa-7,12-diazadispiro[2.1.55.33]tridecane Chemical compound C(C1=CC=CC=C1)N1CC2(OC3(CC3)CN(C2)CC)CCC1 NGYHVFUTMMQVBC-UHFFFAOYSA-N 0.000 claims 1
- AVFCESSCMFFFHS-UHFFFAOYSA-N 7-benzyl-12-phenyl-4-oxa-7,12-diazadispiro[2.1.55.33]tridecan-13-one Chemical compound C(C1=CC=CC=C1)N1CC2(OC3(CC3)C(N(C2)C2=CC=CC=C2)=O)CCC1 AVFCESSCMFFFHS-UHFFFAOYSA-N 0.000 claims 1
- WJWLJXWEFAHFIT-UHFFFAOYSA-N 7-benzyl-12-phenyl-4-oxa-7,12-diazadispiro[2.1.55.33]tridecane Chemical compound C(N1CCCC2(C1)CN(CC1(CC1)O2)c1ccccc1)c1ccccc1 WJWLJXWEFAHFIT-UHFFFAOYSA-N 0.000 claims 1
- ILSLOJDPFGOTPQ-UHFFFAOYSA-N 8,13-dibenzyl-4-oxa-8,13-diazadispiro[2.1.65.33]tetradecane Chemical compound C(N1CC2(CC2)OC2(C1)CCCN(Cc1ccccc1)CC2)c1ccccc1 ILSLOJDPFGOTPQ-UHFFFAOYSA-N 0.000 claims 1
- QWSIPIQPBSXGNU-UHFFFAOYSA-N 8-(3-methylbutyl)-13-phenyl-4-oxa-8,13-diazadispiro[2.1.65.33]tetradecan-14-one Chemical compound C(CC(C)C)N1CCC2(OC3(CC3)C(N(C2)C2=CC=CC=C2)=O)CCC1 QWSIPIQPBSXGNU-UHFFFAOYSA-N 0.000 claims 1
- NTQSHNXXTDSJJE-UHFFFAOYSA-N 8-[(4-fluorophenyl)methyl]-13-methyl-4-oxa-8,13-diazadispiro[2.1.65.33]tetradecan-14-one Chemical compound CN1CC2(CCCN(Cc3ccc(F)cc3)CC2)OC2(CC2)C1=O NTQSHNXXTDSJJE-UHFFFAOYSA-N 0.000 claims 1
- NBGKEOUVHIEVLT-UHFFFAOYSA-N 8-benzyl-13-ethyl-4-oxa-8,13-diazadispiro[2.1.65.33]tetradecan-14-one Chemical compound C(C1=CC=CC=C1)N1CCC2(OC3(CC3)C(N(C2)CC)=O)CCC1 NBGKEOUVHIEVLT-UHFFFAOYSA-N 0.000 claims 1
- WSJSLQGRPCUPFR-UHFFFAOYSA-N 8-benzyl-13-methyl-4-oxa-8,13-diazadispiro[2.1.65.33]tetradecan-14-one Chemical compound CN1CC2(CCCN(Cc3ccccc3)CC2)OC2(CC2)C1=O WSJSLQGRPCUPFR-UHFFFAOYSA-N 0.000 claims 1
- GRCOYZXDTAEHBR-UHFFFAOYSA-N 8-benzyl-13-phenyl-4-oxa-8,13-diazadispiro[2.1.65.33]tetradecan-14-one Chemical compound C(C1=CC=CC=C1)N1CCC2(OC3(CC3)C(N(C2)C2=CC=CC=C2)=O)CCC1 GRCOYZXDTAEHBR-UHFFFAOYSA-N 0.000 claims 1
- LGNJZQOLDIBCGR-UHFFFAOYSA-N 8-benzyl-13-phenyl-4-oxa-8,13-diazadispiro[2.1.65.33]tetradecane Chemical compound C(C1=CC=CC=C1)N1CCC2(OC3(CC3)CN(C2)C2=CC=CC=C2)CCC1 LGNJZQOLDIBCGR-UHFFFAOYSA-N 0.000 claims 1
- BTDKGMFDSQZHST-LBPRGKRZSA-N C(C)N1C([C@@H](OC2(CN(C2)CCC(C)C)C1)C)=O Chemical compound C(C)N1C([C@@H](OC2(CN(C2)CCC(C)C)C1)C)=O BTDKGMFDSQZHST-LBPRGKRZSA-N 0.000 claims 1
- BTDKGMFDSQZHST-GFCCVEGCSA-N C(C)N1C([C@H](OC2(CN(C2)CCC(C)C)C1)C)=O Chemical compound C(C)N1C([C@H](OC2(CN(C2)CCC(C)C)C1)C)=O BTDKGMFDSQZHST-GFCCVEGCSA-N 0.000 claims 1
- YYLPDSFHMKRZDB-OXQOHEQNSA-N C(C)N1C([C@H](O[C@@]2(C1)CCN(CCC2)CC1=CC=C(C#N)C=C1)C)=O Chemical compound C(C)N1C([C@H](O[C@@]2(C1)CCN(CCC2)CC1=CC=C(C#N)C=C1)C)=O YYLPDSFHMKRZDB-OXQOHEQNSA-N 0.000 claims 1
- YYLPDSFHMKRZDB-UZLBHIALSA-N C(C)N1C([C@H](O[C@]2(C1)CCN(CCC2)CC1=CC=C(C#N)C=C1)C)=O Chemical compound C(C)N1C([C@H](O[C@]2(C1)CCN(CCC2)CC1=CC=C(C#N)C=C1)C)=O YYLPDSFHMKRZDB-UZLBHIALSA-N 0.000 claims 1
- QCEAFOWTOSWFHK-WBVHZDCISA-N C(C)N1C([C@H](O[C@]2(C1)CCN(CCC2)CCC(C)C)C)=O Chemical compound C(C)N1C([C@H](O[C@]2(C1)CCN(CCC2)CCC(C)C)C)=O QCEAFOWTOSWFHK-WBVHZDCISA-N 0.000 claims 1
- MRWSXVUXFOTTJR-UHFFFAOYSA-N C(C)N1CC2(OC3(CC3)C1=O)CN(C2)CCOC(C)C Chemical compound C(C)N1CC2(OC3(CC3)C1=O)CN(C2)CCOC(C)C MRWSXVUXFOTTJR-UHFFFAOYSA-N 0.000 claims 1
- CAUNAQZVIDJRRL-UHFFFAOYSA-N CCN1CC2(CC2)OC2(C1)CCCN(CCC(C)C)CC2 Chemical compound CCN1CC2(CC2)OC2(C1)CCCN(CCC(C)C)CC2 CAUNAQZVIDJRRL-UHFFFAOYSA-N 0.000 claims 1
- 206010058019 Cancer Pain Diseases 0.000 claims 1
- 208000000094 Chronic Pain Diseases 0.000 claims 1
- 208000035154 Hyperesthesia Diseases 0.000 claims 1
- 206010065390 Inflammatory pain Diseases 0.000 claims 1
- 208000019695 Migraine disease Diseases 0.000 claims 1
- LCDDJLCGRUCLEJ-JOCHJYFZSA-N [(5R)-8-(3-methylbutyl)-4-oxa-8,13-diazadispiro[2.1.65.33]tetradecan-13-yl]-phenylmethanone Chemical compound C(CC(C)C)N1CC[C@]2(OC3(CC3)CN(C2)C(=O)C2=CC=CC=C2)CCC1 LCDDJLCGRUCLEJ-JOCHJYFZSA-N 0.000 claims 1
- LCDDJLCGRUCLEJ-QFIPXVFZSA-N [(5S)-8-(3-methylbutyl)-4-oxa-8,13-diazadispiro[2.1.65.33]tetradecan-13-yl]-phenylmethanone Chemical compound C(CC(C)C)N1CC[C@@]2(OC3(CC3)CN(C2)C(=O)C2=CC=CC=C2)CCC1 LCDDJLCGRUCLEJ-QFIPXVFZSA-N 0.000 claims 1
- AVYCAHLIVKLAHU-AREMUKBSSA-N [(6R)-2,2-dimethyl-10-(2-phenylethyl)-1-oxa-4,10-diazaspiro[5.6]dodecan-4-yl]-phenylmethanone Chemical compound CC1(C)CN(C[C@]2(CCCN(CCc3ccccc3)CC2)O1)C(=O)c1ccccc1 AVYCAHLIVKLAHU-AREMUKBSSA-N 0.000 claims 1
- AVYCAHLIVKLAHU-SANMLTNESA-N [(6S)-2,2-dimethyl-10-(2-phenylethyl)-1-oxa-4,10-diazaspiro[5.6]dodecan-4-yl]-phenylmethanone Chemical compound CC1(O[C@]2(CN(C1)C(=O)C1=CC=CC=C1)CCN(CCC2)CCC1=CC=CC=C1)C AVYCAHLIVKLAHU-SANMLTNESA-N 0.000 claims 1
- AVYCAHLIVKLAHU-UHFFFAOYSA-N [2,2-dimethyl-10-(2-phenylethyl)-1-oxa-4,10-diazaspiro[5.6]dodecan-4-yl]-phenylmethanone Chemical compound CC1(C)CN(CC2(CCCN(CCc3ccccc3)CC2)O1)C(=O)c1ccccc1 AVYCAHLIVKLAHU-UHFFFAOYSA-N 0.000 claims 1
- YYSVTTBNRFEHRW-UHFFFAOYSA-N [2,2-dimethyl-10-(2-propan-2-yloxyethyl)-1-oxa-4,10-diazaspiro[5.6]dodecan-4-yl]-phenylmethanone Chemical compound CC(C)OCCN1CCCC2(CN(CC(C)(C)O2)C(=O)c2ccccc2)CC1 YYSVTTBNRFEHRW-UHFFFAOYSA-N 0.000 claims 1
- PKKGYWKHJQCTKO-UHFFFAOYSA-N [7-(2-methylpropyl)-4-oxa-7,12-diazadispiro[2.1.55.33]tridecan-12-yl]-phenylmethanone Chemical compound CC(C)CN1CCCC2(C1)CN(CC1(CC1)O2)C(=O)c1ccccc1 PKKGYWKHJQCTKO-UHFFFAOYSA-N 0.000 claims 1
- BJHCENNCJVUEHT-UHFFFAOYSA-N [7-(3-methylbutyl)-4-oxa-7,12-diazadispiro[2.1.55.33]tridecan-12-yl]-phenylmethanone Chemical compound CC(C)CCN1CCCC2(C1)CN(CC1(CC1)O2)C(=O)c1ccccc1 BJHCENNCJVUEHT-UHFFFAOYSA-N 0.000 claims 1
- GDODHTFXEDYIJW-UHFFFAOYSA-N [8-(2-methylpropyl)-4-oxa-8,13-diazadispiro[2.1.65.33]tetradecan-13-yl]-phenylmethanone Chemical compound CC(C)CN1CCCC2(CN(CC3(CC3)O2)C(=O)c2ccccc2)CC1 GDODHTFXEDYIJW-UHFFFAOYSA-N 0.000 claims 1
- LCDDJLCGRUCLEJ-UHFFFAOYSA-N [8-(3-methylbutyl)-4-oxa-8,13-diazadispiro[2.1.65.33]tetradecan-13-yl]-phenylmethanone Chemical compound CC(C)CCN1CCCC2(CN(CC3(CC3)O2)C(=O)c2ccccc2)CC1 LCDDJLCGRUCLEJ-UHFFFAOYSA-N 0.000 claims 1
- 208000005298 acute pain Diseases 0.000 claims 1
- 239000002671 adjuvant Substances 0.000 claims 1
- 150000001299 aldehydes Chemical class 0.000 claims 1
- 125000003342 alkenyl group Chemical group 0.000 claims 1
- 125000000304 alkynyl group Chemical group 0.000 claims 1
- 206010053552 allodynia Diseases 0.000 claims 1
- 238000005888 cyclopropanation reaction Methods 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 1
- 238000003402 intramolecular cyclocondensation reaction Methods 0.000 claims 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 1
- 206010027599 migraine Diseases 0.000 claims 1
- 239000000203 mixture Substances 0.000 claims 1
- 208000004296 neuralgia Diseases 0.000 claims 1
- 208000021722 neuropathic pain Diseases 0.000 claims 1
- 239000000825 pharmaceutical preparation Substances 0.000 claims 1
- XJGOWLUDIUEFQE-UHFFFAOYSA-N phenyl-[7-(2-phenylethyl)-4-oxa-7,10-diazadispiro[2.1.35.33]undecan-10-yl]methanone Chemical compound O=C(N1CC2(CC2)OC2(CN(CCc3ccccc3)C2)C1)c1ccccc1 XJGOWLUDIUEFQE-UHFFFAOYSA-N 0.000 claims 1
- UUEBVOLOOMUGEQ-UHFFFAOYSA-N phenyl-[7-(2-phenylethyl)-4-oxa-7,12-diazadispiro[2.1.55.33]tridecan-12-yl]methanone Chemical compound O=C(N1CC2(CC2)OC2(CCCN(CCc3ccccc3)C2)C1)c1ccccc1 UUEBVOLOOMUGEQ-UHFFFAOYSA-N 0.000 claims 1
- WNYNLIQSXATXOK-UHFFFAOYSA-N phenyl-[8-(2-phenylethyl)-4-oxa-8,13-diazadispiro[2.1.65.33]tetradecan-13-yl]methanone Chemical compound O=C(N1CC2(CC2)OC2(C1)CCCN(CCc1ccccc1)CC2)c1ccccc1 WNYNLIQSXATXOK-UHFFFAOYSA-N 0.000 claims 1
- 238000006268 reductive amination reaction Methods 0.000 claims 1
- 239000012453 solvate Substances 0.000 claims 1
- 208000009935 visceral pain Diseases 0.000 claims 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D498/10—Spiro-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/42—Oxazoles
- A61K31/424—Oxazoles condensed with heterocyclic ring systems, e.g. clavulanic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pain & Pain Management (AREA)
- Epidemiology (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Claims (17)
1. Spoj s općom Formulom (I):
[image]
pri čemu
R1 je
[image]
m je 1, 2, 3, 4 ili 5;
n je 0, 1, 2, 3, 4 ili 5;
p je 0 ili 1;
q je 0, 1 ili 2;
r je 0, 1 ili 2;
X je veza, -C(RxRx')-, -C(O)-, -O-, -C(O)NR7-, -NR7C(O)- ili -C(O)O-;
pri čemu Rx se bira iz niza koji sadrži halogen ili supstituirani ili nesupstituirani C1-6 alkil, supstituirani ili nesupstituirani C2-6 alkenil supstituirani ili nesupstituirani C2-6 alkinil, i -OR7;
Rx' se bira iz niza koji sadrži vodik, halogen ili supstituirani ili nesupstituirani C1-6 alkil, supstituirani ili nesupstituirani C2-6 alkenil i supstituirani ili nesupstituirani C2-6alkinil;
R7 se bira iz niza koji sadrži vodik, supstituirani ili nesupstituirani C1-6 alkil, supstituirani ili nesupstituirani C2-6 alkenil i supstituirani ili nesupstituirani C2-6 alkinil;
Y je -CH2- ili -C(O)-;
R1' se bira iz niza koji sadrži supstituirani ili nesupstituirani C1-6 alkil, supstituirani ili nesupstituirani C2-6 alkenil, supstituirani ili nesupstituirani C2-6 alkinil, supstituirani ili nesupstituirani cikloalkil, supstituirani ili nesupstituirani aril i supstituirani ili nesupstituirani heterociklil;
R2 se bira iz niza koji sadrži vodik, supstituirani ili nesupstituirani C1-6 alkil, supstituirani ili nesupstituirani C2-6 alkenil, supstituirani ili nesupstituirani C2-6 alkinil, supstituirani ili nesupstituirani cikloalkil, supstituirani ili nesupstituirani aril i supstituirani ili nesupstituirani heterociklil,
R3 se bira iz niza koji sadrži supstituirani ili nesupstituirani C1-6 alkil, supstituirani ili nesupstituirani C2-6 alkenil i supstituirani ili nesupstituirani C2-6 alkinil;
R3' se bira iz niza koji sadrži vodik, supstituirani ili nesupstituirani C1-6 alkil, supstituirani ili nesupstituirani C2-6 alkenil i supstituirani ili nesupstituirani C2-6 alkinil;
alternativno, R3 i R3' mogu tvoriti zajedno s ugljikovim atomom na koji su oni vezani supstituirani ili nesupstituirani cikloalkil;
R4 i R4' su neovisno odabrani iz niza koji sadrži vodik, supstituirani ili nesupstituirani C1-6 alkil, supstituirani ili nesupstituirani C2-6 alkenil, supstituirani ili nesupstituirani C2-6 alkinil, -CHOR9 i -C(O)OR9;
pri čemu R9 se bira iz niza koji sadrži vodik, supstituirani ili nesupstituirani C1-9 alkil, supstituirani ili nesupstituirani C2-9 alkenil i supstituirani ili nesupstituirani C2-9 alkinil;
R5 i R5' su neovisno odabrani iz niza koji sadrži vodik, supstituirani ili nesupstituirani C1-6 alkil, supstituirani ili nesupstituirani C2-6 alkenil, supstituirani ili nesupstituirani C2-6 alkinil, supstituirani ili nesupstituirani cikloalkil, supstituirani ili nesupstituirani aril, supstituirani ili nesupstituirani heterociklil, -CHOR8 i - C(O)OR8;
pri čemu R8 se bira iz niza koji sadrži vodik, supstituirani ili nesupstituirani C1-6 alkil, supstituirani ili nesupstituirani C2-6 alkenil i supstituirani ili nesupstituirani C2-6 alkinil;
alternativno R5 i R5' uzeti zajedno s povezujućim C-atomom mogu tvoriti supstituirani ili nesupstituirani cikloalkil ili supstituirani ili nesupstituirani heterociklil;
R6 i R6' su neovisno odabrani iz niza koji sadrži vodik, supstituirani ili nesupstituirani C1-6 alkil, supstituirani ili nesupstituirani C2-6 alkenil, supstituirani ili nesupstituirani C2-6 alkinil, -CHOR10 i -C(O)OR10;
pri čemu R10 se bira iz niza koji sadrži vodik, supstituirani ili nesupstituirani C1-6 alkil, supstituirani ili nesupstituirani C2-6 alkenil i supstituirani ili nesupstituirani C2-6 alkinil;
proizvoljno u obliku jednog od stereoizomera, poželjno enantiomera ili dijastereomera, racemata ili u obliku smjese najmanje dva stereoizomera, poželjno enantiomera i/ili dijastereomera, u bilo kojem omjeru miješanja, ili njihove odgovarajuće soli, ili njihov odgovarajući solvat;
uz slijedeće uvjete primjene:
• q nije 1 kada r je 1;
• kada Y je -C(O)-, tada R1 nije
[image]
2. Spoj prema patentnom zahtjevu 1 naznačen time što spoj s Formulom (I) je spoj s Formulom (I')
[image]
3. Spoj prema patentnim zahtjevima 1 ili 2 naznačen time što spoj s Formulom (I) je spoj s Formulom (I2'), (I2a'), (I2b') ili (I2c')
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4. Spoj prema bilo kojem od patentnih zahtjeva 1 do 3 naznačen time što spoj s Formulom (I) je spoj s Formulom (I3'), (I3a'), (I3b') ili (I3c')
[image]
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5. Spoj prema bilo kojem od patentnih zahtjeva 1 do 3 naznačen time što spoj s Formulom (I) je spoj s Formulom (I4'), (I4a'), (I4b') ili (I4c')
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[image]
[image]
6. Spoj prema bilo kojem od patentnih zahtjeva 1 do 5 naznačen time što
R1' se bira iz niza koji sadrži supstituirani ili nesupstituirani C1-6 alkil i supstituirani ili nesupstituirani aril, poželjno supstituirani ili nesupstituirani metil, poželjno supstituirani ili nesupstituirani etil ili poželjno supstituirani ili nesupstituirani fenil.
7. Spoj prema bilo kojem od patentnih zahtjeva 1 do 6 naznačen time što
R2 se bira iz niza koji sadrži supstituirani ili nesupstituirani C1-6 alkil i supstituirani ili nesupstituirani aril, poželjno supstituirani ili nesupstituirani izopropil, supstituirani ili nesupstituirani izobutil ili supstituirani ili nesupstituirani fenil.
8. Spoj prema bilo kojem od patentnih zahtjeva 1 do 7 naznačen time što
R3 i R3' tvore zajedno s ugljikovim atomom na koji su oni vezani supstituirani ili nesupstituirani cikloalkil, poželjno supstituirani ili nesupstituirani C3-6 cikloalkil, poželjno supstituirani ili nesupstituirani ciklopropil.
9. Spoj prema bilo kojem od patentnih zahtjeva 1 do 8 naznačen time što je spoj odabran sa slijedećeg popisa
• 12-etil-7-izopentil-4-oksa-7,12-diazadispiro[2.1.5.3]tridekan-13-on
• 12-etil-7-fenetil-4-oksa-7,12-diazadispiro[2.1.5.3]tridekan-13-on
• 13-etil-8-fenetil-4-oksa-8,13-diazadispiro[2.1.6.3]tetradekan-14-on
• 13-etil-8-izopentil-4-oksa-8,13-diazadispiro[2.1.6.3]tetradekan-14-on
• 7-benzil-10-etil-4-oksa-7,10-diazadispiro[2.1.3.3]undekan-11-on
• 10-etil-7-izopentil-4-oksa-7,10-diazadispiro[2.1.3.3]undekan-11-on
• 7-fenetil-12-fenil-4-oksa-7,12-diazadispiro[2.1.5.3]tridekan-13-on
• 7-izopentil-12-fenil-4-oksa-7,12-diazadispiro[2.1.5.3]tridekan-13-on
• 8-fenetil-13-fenil-4-oksa-8,13-diazadispiro[2.1.6.3]tetradekan-14-on
• 8-izopentil-13-fenil-4-oksa-8,13-diazadispiro[2.1.6.3]tetradekan-14-on
• 7-benzil-12-etil-4-oksa-7,12-diazadispiro[2.1.5.3]tridekan-13-on
• 8-benzil-13-etil-4-oksa-8,13-diazadispiro[2.1.6.3]tetradekan-14-on
• 7-benzil-10-etil-4-oksa-7,10-diazadispiro[2.1.3.3]undekan-11-on
• 8-benzil-13-fenil-4-oksa-8,13-diazadispiro[2.1.6.3]tetradekan-14-on
• 7-benzil-12-fenil-4-oksa-7,12-diazadispiro[2.1.5.3]tridekan-13-on
• 13-etil-8-fenetil-4-oksa-8,13-diazadispiro[2.1.6.3]tetradekan
• 7-benzil-12-etil-4-oksa-7,12-diazadispiro[2.1.5.3]tridekan
• 12-etil-7-fenetil-4-oksa-7,12-diazadispiro[2.1.5.3]tridekan
• 7-fenetil-12-fenil-4-oksa-7,12-diazadispiro[2.1.5.3]tridekan
• 7-izopentil-12-fenil-4-oksa-7,12-diazadispiro[2.1.5.3]tridekan
• 8-benzil-13-fenil-4-oksa-8,13-diazadispiro[2.1.6.3]tetradekan
• 8-fenetil-13-fenil-4-oksa-8,13-diazadispiro[2.1.6.3]tetradekan.
10. Spoj prema bilo kojem od patentnih zahtjeva 1 do 8 naznačen time što je spoj odabran sa slijedećeg popisa
23 7-benzil-12-fenil-4-oksa-7, 12-diazadispiro[2.1.5.3]tridekan
24 (7-fenetil-4-oksa-7,12-diazadispiro[2.1.5.3]tridekan-12-il)(fenil)metanon
25 (7-izopentil-4-oksa-7,12-diazadispiro[2.1.5.3]tridekan-12-il)(fenil)metanon
26 (7-izobutil-4-oksa-7,12-diazadispiro[2.1.5.3]tridekan-12-il)(fenil)metanon
27 (8-fenetil-4-oksa-8,13-diazadispiro[2.1.6.3]tetradekan-13-il)(fenil)metanon
28 (8-izopentil-4-oksa-8,13-diazadispiro[2.1.6.3]tetradekan-13-il)(fenil)metanon
29 (8-izobutil-4-oksa-8,13-diazadispiro[2.1.6.3]tetradekan-13-il)(fenil)metanon
30 4-etil-2,2-dimetil-9-fenetil-1-oksa-4,9-diazaspiro[5.6]dodekan-3-on
31 4-etil-9-izopentil-2,2-dimetil-1-oksa-4,9-diazaspiro[5.6]dodekan-3-on
32 4-etil-9-izobutil-2,2-dimetil-1-oksa-4,9-diazaspiro[5.6]dodekan-3-on
33 10-benzil-7-fenetil-4-oksa-7,10-diazadispiro[2.1.3.3]undekan-11-on
34 (2,2-dimetil-9-fenetil-1-oksa-4,9-diazaspiro[5.6]dodekan-4-il)(fenil)metanon
35 10-etil-7-(2-izopropoksietil)-4-oksa-7,10-diazadispiro[2.1.3.3]undekan-11-on
36 (R)-8-etil-2-izopentil-6-metil-5-oksa-2,8-diazaspiro[3.5]nonan-7-on
37 (S)-8-etil-2-izopentil-6-metil-5-oksa-2,8-diazaspiro[3.5]nonan-7-on
38 (R)-8-etil-2-izobutil-6-metil-5-oksa-2,8-diazaspiro[3.5]nonan-7-on
39 (S)-8-etil-2-izobutil-6-metil-5-oksa-2,8-diazaspiro[3.5]nonan-7-on
40 (R)-2-izopentil-8-izopropil-6-metil-5-oksa-2,8-diazaspiro[3.5]nonan-7-on
41 (S)-2-izopentil-8-izopropil-6-metil-5-oksa-2,8-diazaspiro[3.5]nonan-7-on
42 (R)-2-izobutil-8-izopropil-6-metil-5-oksa-2, 8-diazaspiro[3.5]nonan-7-on
43 (S)-2-izobutil-8-izopropil-6-metil-5-oksa-2, 8-diazaspiro[3.5]nonan-7-on
44 (S)-2-(3,3-dimetilbutil)-8-izopropil-6-metil-5-oksa-2,8-diazaspiro[3.5]nonan-7-on
45 (R)-2-(3,3-dimetilbutil)-8-izopropil-6-metil-5-oksa-2, 8-diazaspiro[3.5]nonan-7-on
46 (2R,6S)-4-etil-9-izopentil-2-metil-1-oksa-4,9-diazaspiro[5.6]dodekan-3-on
47 (2R,6R)-4-etil-9-izopentil-2-metil-1-oksa-4,9-diazaspiro[5.6]dodekan-3-on
48 (2S,6S)-4-etil-9-izopentil-2-metil-1-oksa-4,9-diazaspiro[5.6]dodekan-3-on
49 (2S,6R)-4-etil-9-izopentil-2-metil-1-oksa-4,9-diazaspiro[5.6]dodekan-3-on
50 (9-(2-izopropoksietil)-2,2-dimetil-1-oksa-4,9-diazaspiro[5.6]dodekan-4-il)(fenil)metanon
55 (7-benzil-4-oksa-7,12-diazadispiro[2.1.5.3]tridekan-12-il)(fenil)metanon
56 (8-benzil-4-oksa-8,13-diazadispiro[2.1.6.3]tetradekan-13-il)(fenil)metanon
57 9-benzil-4-etil-2,2-dimetil-1-oksa-4,9-diazaspiro[5.6]dodekan-3-on
58 4-((4-etil-2,2-dimetil-3-okso-1-oksa-4,9-diazaspiro[5.6]dodekan-9-il)metil)benzonitril
59 (2R,6S)-9-benzil-4-etil-2-metil-1-oksa-4,9-diazaspiro[5.6]dodekan-3-on
60 (2R,6R)-9-benzil-4-etil-2-metil-1-oksa-4,9-diazaspiro[5.6]dodekan-3-on
61 (2S,6S)-9-benzil-4-etil-2-metil-1-oksa-4,9-diazaspiro[5.6]dodekan-3-on
62 (2S,6R)-9-benzil-4-etil-2-metil-1-oksa-4, 9-diazaspiro[5.6]dodekan-3-on
63 (2R,6S)-4-etil-9-(4-fluorobenzil)-2-metil-1-oksa-4,9-diazaspiro[5.6]dodekan-3-on
64 (2R,6R)-4-etil-9-(4-fluorobenzil)-2-metil-1-oksa-4,9-diazaspiro[5.6]dodekan-3-on
65 (2S,6S)-4-etil-9-(4-fluorobenzil)-2-metil-1-oksa-4,9-diazaspiro[5.6]dodekan-3-on
66 (2S,6R)-4-etil-9-(4-fluorobenzil)-2-metil-1-oksa-4,9-diazaspiro[5.6]dodekan-3-on
67 4-(((2R,6S)-4-etil-2-metil-3-okso-1-oksa-4,9-diazaspiro[5.6]dodekan-9-il)metil)benzonitril
68 4-(((2R,6R)-4-etil-2-metil-3-okso-1-oksa-4,9-diazaspiro[5.6]dodekan-9-il)metil)benzonitril
69 4-(((2S,6S)-4-etil-2-metil-3-okso-1-oksa-4,9-diazaspiro[5.6]dodekan-9-il)metil)benzonitril
70 4-(((2S,6R)-4-etil-2-metil-3-okso-1-oksa-4,9-diazaspiro[5.6]dodekan-9-il)metil)benzonitril
71 8-benzil-13-metil-4-oksa-8,13-diazadispiro[2.1.6.3]tetradekan-14-on
72 8-(4-fluorobenzil)-13-metil-4-oksa-8,13-diazadispiro[2.1.6.3]tetradekan-14-on
73 4-((13-metil-14-okso-4-oksa-8,13-diazadispiro[2.1.6.3]tetradekan-8-il)metil)benzonitril
74 (S)-8-etil-6-metil-2-neopentil-5-oksa-2,8-diazaspiro[3.5]nonan-7-on
75 (R)-8-etil-6-metil-2-neopentil-5-oksa-2,8-diazaspiro[3.5]nonan-7-on
76 (S)-8-izopropil-6-metil-2-neopentil-5-oksa-2,8-diazaspiro[3.5]nonan-7-on
77 (R)-8-izopropil-6-metil-2-neopentil-5-oksa-2, 8-diazaspiro[3.5]nonan-7-on
78 7,12-dibenzil-4-oksa-7,12-diazadispiro[2.1.5.3]tridekan(*)
79 12-benzil-7-fenetil-4-oksa-7,12-diazadispiro[2.1.5.3]tridekan(*)
80 12-benzil-7-izopentil-4-oksa-7,12-diazadispiro[2.1.5.3]tridekan(*)
81 12-benzil-7-izobutil-4-oksa-7,12-diazadispiro[2.1.5.3]tridekan(*)
82 8,13-dibenzil-4-oksa-8,13-diazadispiro[2.1.6.3]tetradekan(*)
83 13-benzil-8-fenetil-4-oksa-8,13-diazadispiro[2.1.6.3]tetradekan(*)
84 13-benzil-8-izopentil-4-oksa-8,13-diazadispiro[2.1.6.3]tetradekan(*)
85 13-benzil-8-izobutil-4-oksa-8,13-diazadispiro[2.1.6.3]tetradekan(*)
86 9-benzil-4-etil-2,2-dimetil-1-oksa-4,9-diazaspiro[5.6]dodekan
87 4-etil-2,2-dimetil-9-fenetil-1-oksa-4,9-diazaspiro[5.6]dodekan
88 4-etil-9-izopentil-2,2-dimetil-1-oksa-4,9-diazaspiro[5.6]dodekan
89 4-etil-9-izobutil-2,2-dimetil-1-oksa-4,9-diazaspiro[5.6]dodekan
90 10-benzil-7-fenetil-4-oksa-7,10-diazadispiro[2.1.3.3]undekan
91 (7-Fenetil-4-oksa-7,10-diazadispiro[2.1.3.3]undekan-10-il)(fenil)metanon
92 (R)-8-benzil-13-etil-4-oksa-8,13-diazadispiro[2.1.6.3]tetradekan-14-on
93 (S)-8-benzil-13-etil-4-oksa-8,13-diazadispiro[2.1.6.3]tetradekan-14-on
94 (R)-(2,2-dimetil-9-fenetil-1-oksa-4,9-diazaspiro[5.6]dodekan-4-il)(fenil)metanon
95 (S)-(2,2-dimetil-9-fenetil-1-oksa-4,9-diazaspiro[5.6]dodekan-4-il)(fenil)metanon
11. Spoj prema bilo kojem od patentnih zahtjeva 1 do 8 naznačen time što je spoj odabran sa slijedećeg popisa
51 ((2S,6R)-9-izopentil-2-metil-1-oksa-4,9-diazaspiro[5.6]dodekan-4-il)(fenil)metanon
52 ((2S,6S)-9-izopentil-2-metil-1-oksa-4,9-diazaspiro[5.6]dodekan-4-il)(fenil)metanon
53 ((2R,6R)-9-izopentil-2-metil-1-oksa-4,9-diazaspiro[5.6]dodekan-4-il)(fenil)metanon
54 ((2R,6S)-9-izopentil-2-metil-1-oksa-4,9-diazaspiro[5.6]dodekan-4-il)(fenil)metanon
96 (R)-(8-izopentil-4-oksa-8,13-diazadispiro[2.1.6.3]tetradekan-13-il)(fenil)metanon
97 (S)-(8-izopentil-4-oksa-8,13-diazadispiro[2.1.6.3]tetradekan-13-il)(fenil)metanon
12. Postupak za pripravu spoja s Formulom (I) kako je definirano u bilo kojem od patentnih zahtjeva 1 do 11 pri čemu R1 je -(CR4R4')pR1', te navedeni postupak sadrži:
a) intramolekularnu ciklizaciju spoja s Formulom VIIa
[image]
ili
b) reakciju spoja s Formulom VIIIH
[image]
sa spojem s Formulom IX, X ili XI,
[image]
ili
c1) kada Y je CH2, alkilacijom spoja s Formulom XIV
[image]
sa spojem s Formulom XV
[image]
spoj s Formulom XV je alkilirajuće sredstvo i V izlazna skupina, ili alternativno reakcijom reduktivne aminacije spoja s Formulom XIV sa spojem s Formulom XV, spoj s Formulom XV je aldehid i V je C(O)H skupina;
ili
c2) kada Y je C(O), alkilacijom spoja s Formulom XIV
[image]
sa spojem s Formulom XV
[image]
spoj s Formulom XV je alkilirajuće sredstvo i V izlazna skupina.
13. Postupak za pripravu spoja s Formulom (I) kako je definirano u bilo kojem od patentnih zahtjeva 1 do 11 pri čemu R1 je -(CR4R4')pR1', Y predstavlja CO i R3 i R3' uzeti zajedno s povezujućim C-atomom tvore ciklopropil (spojevi s formulom Id),
[image]
navedeni postupak sadrži
a) obradom s jakom bazom spoja s Formulom Ic pri čemu Rs=Rs'=H i s=1
[image]
ili
b) reakcijom ciklopropanacije na spoju s Formulom XXXI
[image]
ili
c) alkilacijom spoja s Formulom XXV
[image]
sa spojem s Formulom XV
[image]
spoj s Formulom XV je alkilirajuće sredstvo i V izlazna skupina;
ili
d) reakcijom spoja s Formulom XIXH
[image]
sa spojem s Formulom IX, X ili XI,
[image]
14. Upotreba spojeva s Formulama II, IIP, III, IIIP, IVa, IVb, Vb, VbP, XII, XIIP, Va, VaP, VI, VIIb, VIIbP, XIII, XIIIP, VIIa, VIIaP, XVI, XVIP, XVIH, XIV, XIVP, XIVH, Ia, VIIIP, VIIIH, XV, IX, X, XI, Ie, XXP, XXH, XXI, XXIP, XXIH, Ib, XVIIP, XVIIH, Ic, XVIIIP, Id, XIXP, XIXH, XXIII, XIIIP, XIIIH, XXV, XXVP, XXVH, XXII, XXIIP, XXIIH, XXIV, XXIVP, XXIVH, If, XXVIP, XXVIH, XXVIIa, Ig, XXVIIIP, XXVIIH, XXVIIb, Ih, XXIXP, XXIXH, XXVIIc, Ib, XVIIP, XVIIH, XXXII, XXXIIP, XXXIIH, XXXIV, XXXIVP, XXXIVH, XXXI, XXXIP, XXXIH, XXXIII, XXXIIIP, XXXIIIH, XXXV, Ij, XXXVIP, XXXVIH, Ih, XXIXP, XXIXH, Ii, XXXP ili XXXH,
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za pripravu spoja s Formulom (I) kako je definirano u bilo kojem od patentnih zahtjeva 1 do 11.
15. Farmaceutski pripravak naznačen time što sadrži spoj s Formulom (I) kako je definirano u bilo kojem od patentnih zahtjeva 1 do 11 ili njegovu farmaceutski prihvatljivu sol, te farmaceutski prihvatljiv nosač, adjuvans ili nosač.
16. Spoj s Formulom (I) kako je definirano u bilo kojem od patentnih zahtjeva 1 do 11 naznačen time što se koristi kao lijek.
17. Spoj s Formulom (I) kako je definirano u bilo kojem od patentnih zahtjeva 1 do 11 naznačen time što se koristi u liječenju bola, naročito srednje do jake boli, visceralne boli, kronične boli, boli zbog raka, migrene, upalne boli, akutne boli ili neuropatske boli, alodinije ili hiperalgezije.
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| PCT/EP2016/001742 WO2017067664A1 (en) | 2015-10-23 | 2016-10-21 | Oxa-diazaspiro compounds having activity against pain |
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| US3481942A (en) | 1968-09-06 | 1969-12-02 | Smithkline Corp | Oxa-diazaspiro(4.5)decane compounds |
| US4353900A (en) * | 1981-10-19 | 1982-10-12 | Syntex (U.S.A.) Inc. | 9-(Arylalkyl or aroylalkyl)-1-oxa-4,9-diazaspiro(5.5)undecan-3-ones |
| WO1993013101A1 (en) * | 1991-12-27 | 1993-07-08 | Yoshitomi Pharmaceutical Industries, Ltd. | Pyridonecarboxylate compound, pharmaceutical use thereof, and spiro compound |
| US6114541A (en) | 1997-03-10 | 2000-09-05 | Hoffmann-La Roche Inc. | Method for the preparation of α-Bromo-Lactam derivatives |
| KR100974901B1 (ko) | 2001-12-28 | 2010-08-10 | 아카디아 파마슈티칼스 인코포레이티드 | 모노아민 수용체 조정자로서의 스피로아자사이클릭 화합물 |
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- 2016-10-21 JP JP2018519862A patent/JP6884973B2/ja active Active
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